[5] DiaPep277 blocks the immune system's destruction of pancreatic beta cells in humans. Scientists at the Weizmann Institute in Rehovot, Israel, have developed the first successful vaccine for Type I diabetes. The vaccine blocks the immune system's destruction of pancreatic beta cells in humans. The drug, DiaPep277, offers the possibility both of preventing the onset of the disease in those with a genetic risk and of halting its progression in those whose cells have already begun to die. With Phase II trials on DiaPep277 successfully completed, Phase III trials are to begin in various centers around the world next year. Peptor Ltd. - the Rehovot biopharmaceutical company that purchased the rights - is planning to present an application to the U.S. Food and Drug Administration in 2004. A team of researchers, led by Weizmann's Irun Cohen, has worked more than 10 years on a small peptide fragment known as p277, despite skepticism among others in the field about its possible efficacy. Results on a mouse model were dramatic, and the team proceeded to show its efficacy on patients, 200 of whom have been treated successfully in Israel and in England, Hungary, Bulgaria and Germany. Based on the results of their research, Peptor developed DiaPep277. Cohen, Dana Elias (then a postdoctoral fellow at Weizmann and now vice president for research and development at Peptor), and colleagues reported on the clinical study performed at Hadassah-University Hospital in Jerusalem's Ein Kerem by Itamar Raz, president of the Israel Diabetes Association and head of the hospital's diabetes unit, in the British journal The Lancet. The researchers proved three injections in six months of DiaPep277 were successful in arresting the progression of Type l diabetes in newly diagnosed patients - without displaying any harmful or significant side effects and without participants leaving the study. Recent data show between 120 million and140 million people suffer from one of the two types of diabetes. Type I (insulin-dependent) usually results from an autoimmune disorder in which the immune system mistakenly attacks the body's insulin-producing pancreatic cells, reducing and ultimately stopping all insulin production. Sufferers need to test their blood sugar levels and inject insulin several times daily. Type II is a metabolic disorder resulting from the body's inability to properly use insulin. Patients with the more severe cases of Type II diabetes must supplement their natural insulin production with insulin injections. The Phase II study was of 35 male patients 16-55 who were newly diagnosed with Type I. Eighteen received injections of DiaPep277 at the beginning of the study, at one month, and at six months; 17 received three injections of a placebo. Those who received DiaPep277 showed a halt or delay in the attack upon, or destruction of, their beta cells when examined at a follow-up 10 months after the first injection. These results were evident in the level of the body's own insulin production and thus a decreased need for insulin injections. The researchers were able to trace the mechanism of this improvement to changes in the patients' immune lymphocytes, called T-cells. Those receiving the placebo showed a significant decline in their natural insulin production and a persistent rise in the need for insulin injections. "The older you are, the slower the progression of beta-cell destruction," Cohen said. In children, the destruction of pancreatic cells is very rapid, taking place even in a few months, Raz said. People at genetic risk for the disease who are exposed to a specific virus, toxic material, or food are likely to develop Type I diabetes. Phase II trials on children seven to 16 showed an improvement, but it was not statistically significant. Younger children are now being tested using this strategy, Elias said. For the past several years, Cohen and his team have been studying the mechanism by which the immune system destroys the insulin-producing pancreatic cells. Working with mice, they discovered a particular protein is closely linked to this destructive process. It acts like an antigen, prompting the immune cells to attack. Further investigation revealed injecting diabetic mice with p277 - a small peptide fragment of the protein - shut down the immune response, preventing the progression of Type I diabetes. The peptide essentially acts to "re-educate" the immune cells, switching off their destructive activity, Cohen said. The idea for using p277 stemmed from the discovery the immune system has different options to choose from in responding to an antigen. It can act to destroy the antigen or protect it from destruction. In this case, it indirectly prevents the pancreatic cells from being destroyed. About 15 agents have been found to halt destruction of beta cells in mice, but none of them worked in humans, Raz said. "No one believed it would work in people," he said. Peptor, which was established in 1993, now has 51 employees in Israel and in Germany. It will soon start preliminary testing on two other peptides, including one for kidney damage due to diabetes.

BACKGROUND: Type 1 diabetes mellitus (T1DM) is a T-cell-mediated autoimmune disease that leads to the destruction of insulin-producing beta cells. Treatment with DiaPep277, a peptide derived from heat-shock protein 60 (hsp60), has been found to slow the deterioration of beta-cell function after clinical onset of diabetes in NOD mice and human adults. Our aim was to evaluate the efficacy and safety of DiaPep277 treatment in attenuating beta-cell destruction in children with recent-onset T1DM.

METHODS: A prospective, randomized, double-blind, phase II design was used. The sample included 30 children (19 males) aged 7-14 years who had been diagnosed with T1DM from 53 to 116 days previously, and had basal C-peptide concentrations above 0.1 nmol/L. The children were randomized to receive subcutaneous injections of 1 mg DiaPep277 (15 patients) or 40 mg mannitol (placebo) at entry and at 1, 6, and 12 months. The duration of follow-up was 18 months. The groups were compared for stimulated C-peptide level, exogenous insulin dose, and HbA1c concentration.

RESULTS: C-peptide levels similarly decreased over time in the DiaPep277- and placebo-treated patients. There was no significant difference in insulin dose or HbA1c concentration between the groups at any time point. No serious drug-related adverse effects were recorded throughout the study period.

CONCLUSIONS: One-year treatment with DiaPep277 at a dosage of 1 mg is safe for use and well tolerated in children with recent-onset T1DM. However, it appears to have no beneficial effect in preserving beta-cell function or improving metabolic control.

[7]http://www.andromedabio.com/clinical_trials.php: DIA-AID 2 is a confirmatory phase III study which began in the first half of 2010. This study is a global clinical trial which will be conducted in Europe, USA, Israel, and Latin America with approximately 450 patients being recruited at more than 100 clinical study sites. To be eligible for the study, potential patients should be between 20 to 45 years of age and within 6 months of diagnosis of type 1 diabetes. Furthermore, the study requires a residual beta cell function when fasting of C-peptide ≥ 0.2nmol/L. Patients will be randomized to 1.0 mg DiaPep277® or placebo with primary endpoint beta cell preservation of function.

Andromeda Biotech Ltd. announces initial results from a pivotal phase III clinical study. The 24-month study was randomized, placebo-controlled, designed to assess the safety and efficacy of DiaPep277®, a novel immunotherapeutic agent for the treatment of newly diagnosed patients with Type 1 Diabetes (T1D). The results from patients who were treated with DiaPep277® show that the study has met its primary endpoint, defined as the change from baseline in C-peptide levels at the end of the study. Significant preservation of C-peptide levels, a marker for assessing endogenous insulin secretion by pancreatic cells, was demonstrated in patients treated with DiaPep277® compared to the placebo arm. The decline in C-peptide levels was more pronounced in the placebo arm than in the treated group. The difference between the arms reached 0.949 nmol/L/20 minutes, (p=0.0374). This difference reflects a relative preservation of 23.4% compared to placebo. Evaluation of the primary endpoint was performed on patients in the modified ITT population who have at least one measurement post baseline. The study also achieved a key secondary endpoint, showing that a greater proportion of DiaPep277® treated patients maintained good diabetic control compared to the placebo, measured by HbA1c levels equal or less than 7% at the end of the study (45.5% versus 35.7%, p =0.035 ). Initial safety data also indicate that DiaPep277® was well tolerated. No major differences in drug-related adverse events were reported between the treatment and placebo groups. Additional analyses of clinical, efficacy and safety data from this study are ongoing. A second confirmatory, global Phase III study with DiaPep277® is currently being conducted at about 120 medical centers in the USA, Canada, Europe, Israel and Argentina. Completion of patient recruitment for this study (450 patients) is anticipated by the first half of 2012. Teva Pharmaceutical Industries Ltd. (NASDAQ: TEVA) took an equity position in Andromeda following interim phase III study results, and has an exclusive worldwide license to the DiaPep277® product. Prof. Itamar Raz, Head Diabetes Unit, Department of Medicine, Hadassah University Hospital, Jerusalem, Chairman of the Scientific Steering Committee of the study notes that “We are very pleased with these top-line results, which indicate an important breakthrough for medical science in the area of immune therapy for patients with Type 1 Diabetes. Preservation of the endogenous insulin secretion, which was corroborated by the clinical outcome of improved control of Hb1Ac, may fulfill the current vast unmet medical need in this field.” Dr. Shlomo Dagan, CEO of Andromeda commented, “We are very excited about the prospect of DiaPep277® bringing new hope to newly diagnosed type 1 diabetes patients and their families, especially after other potential late stage products failed to show significant efficacy in immune intervention.” About the Study: The phase III clinical study included 457 newly diagnosed Type 1 Diabetes patients aged 16-45, randomized into two study groups in a 1:1 ratio. The trial was conducted in 40 medical centers in Europe, Israel and South Africa. All patients recruited to the study received daily insulin therapy adjusted to their daily blood glucose levels. In addition, patients who were randomized in the treatment group were injected subcutaneously with 1 mg of DiaPep277® once every three months for two years. Subjects were evaluated for efficacy, defined as the ability to preserve insulin secretion, using the glucagon stimulation test and the mixed meal tolerance test. The target population for efficacy included subjects who entered the study according to the protocol inclusion and exclusion criteria and received at least 1 dose of study medication (modified ITT population), and have at least one measurement post baseline (338 patients, equally divided between the treated and placebo arms). Other clinical endpoints included glycemic parameters such as HbA1c, insulin daily dose requirement and the number of hypoglycemic events. Clinical and safety parameters were evaluated every three months throughout the two years of the study. About DiaPep277: DiaPep277, a unique peptide of 24 amino acids derived from the sequence of the human heat shock protein 60 (Hsp60), was invented by Prof Irun Cohen and his team at the Weizmann Institute of Science. The peptide acts by modulating the immune system, thus preventing the destruction of pancreatic cells that secrete insulin, and preserving their natural function. Treatment of T1D patients with DiaPep277® may have several medical benefits including slowing the deterioration of the disease, improved metabolic control, reduction of daily insulin dose requirements, and reduction of diabetic complications. To date, there is no therapy able to slow the progressive destruction of insulin secreting pancreatic beta cells in T1D. Initially, DiaPep277® is targeted to treat newly diagnosed T1D adult patients with residual insulin secreting cells. Additional target populations include newly diagnosed children with T1D, patients with a high risk of developing T1D, and T1D patients with slow progressing disease. About Andromeda: Andromeda Biotech Ltd., a subsidiary of Clal Biotechnology Industries Ltd. (TASE: CBI) is focused on the development of an innovative treatment for autoimmune diabetes. Andromeda’s DiaPep277®, currently in Phase III Clinical Studies, is a novel therapeutic approach to treat T1D. For more information about Andromeda Biotech please visit our site: (www.andromedabio.com) or contact Shlomo Dagan, Andromeda Biotech Ltd. Phone: +972 8 938 7777 E-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.